Atypical Microglandular Adenosis Research Articles

Morphologic and immunohistochemical features of carcinoma involving microglandular adenosis of the breast following neoadjuvant chemotherapy.

Microglandular adenosis (MGA)-related lesions, including atypical MGA (AMGA) and carcinoma involving MGA (C-MGA), are characterized by epithelial atypia, negative hormone receptors and HER2 status, and can mimic invasive triple negative breast cancer (TNBC) in core needle biopsies (CNB) resulting in selection for treatment with neoadjuvant chemotherapy (NAC). We identified 12 cases of AMGA and/or C-MGA in post-NAC excision specimens (EXC) and analyzed their morphologic and immunohistochemical (IHC) features. All CNBs were initially diagnosed as containing TNBC. Upon re-review, TNBC was confirmed in 9 cases. In 3 CNBs AMGA and/or C-MGA had been interpreted as TNBC. AMGA was initially recognized in only 1 case but AMGA and/or C-MGA were present in an additional 9 CNBs. At EXC, no residual TNBC was present in 5 of 9 EXCs and all 12 cases showed residual AMGA and/or C-MGA. Similar to conventional MGA, AMGA and C-MGA were positive for S-100, laminin and collagen IV and negative for calponin and p63. Following NAC, these lesions retained their typical staining pattern despite acquiring treatment-related morphologic alterations, most notably of which were areas of single cell growth pattern seen in 8 EXCs. This study is the first to report the effects of NAC on AMGA and C-MGA. Our data showed no response of the AMGA and/or C-MGA following NAC in contrast to the high response rate of conventional TNBC. In particular, the infiltrative single cell pattern of post-NAC MGA-related lesions closely mimicked residual TNBC. The persistence of AMGA and C-MGA following NAC supports the notion that these lesions are distinct from conventional TNBC. Our findings also highlight the challenges in recognizing AMGA and C-MGA in CNBs which may lead to unwarranted treatment with NAC in the absence of conventional TNBC.

Microglandular adenosis is an advanced precursor breast lesion with evidence of molecular progression to matrix-producing metaplastic carcinoma

Microglandular adenosis (MGA) is a rare breast lesion reported to be associated with invasive carcinoma in up to 20% to 30% of cases and has been proposed as a nonobligate precursor to basal-like breast cancers. We identified a case of matrix-producing metaplastic carcinoma with morphologic and immunohistochemical evidence of progression from MGA to atypical MGA, carcinoma in situ, and invasive carcinoma. We performed whole-exome sequencing of each component (MGA, atypical MGA, carcinoma in situ, and cancer) to characterize the mutational landscape of these foci. There was a significant copy number overlap between all foci, including a segmental amplification of the CCND1 locus (partial chromosome 11 trisomy) and MYC (8q24.12-13). Using a bioinformatics approach, we were able to identify 3 putative mutational clusters and recurrent, stop-gain nonsynonymous mutations in both ZNF862 and TP53 that were shared across all foci. Finally, we identified a novel deleterious splice-acceptor site mutation of chr5:5186164 G>T (chromosome 5p15) encoding the gene, ADAMTS16, in the invasive component.

Clinicopathologic features of mammary microglandular adenosis with carcinoma: a study of 5 cases

Objective: To study the clinicopathologic, immunohistochemical features, differential diagnoses and prognosis of mammary microglandular adenosis with carcinoma (MGACA) with micropapillary pattern. Methods: Five cases of MGACA were collected from 2010 to 2016 and reviewed for their clinical, histologic features and outcome.EnVision method were done for S-100 protein, cytokeratin (CK), p63, Calponin, smooth muscle myosin heavy chain (SMMHC), PR, ER and HER2. Results: Histologically, microglandular adenosis(MGA), atypical MGA (AMGA) and invasive carcinoma were seen in all five cases of MGACA. The invasive component was metaplastic carcinoma in one case and ductal in four cases. All epithelial cells were S-100 and CK positive in MGA, AMGA and invasive carcinoma. p63, Calponin and SMMHC negativity confirmed the lack of a myoepithelial cell layer in MGA, AMGA and MGACA. PR was weakly focally positive in one case, but ER and HER2 were negative in all cases (four cases were triple negative). Ki-67 index was 20% to 40%. Laminin and collagen Ⅳ staining showed the presence of basement membrane in MGA and AMGA, except MGACA. The follow-up time ranged from 3 months to 6 years, and all patients were alive without recurrence or distant metastasis. Conclusions: MGACA is a rare tumor with distinct morphological and IHC features. Compared to most triple-negative breast cancers, MGACA seems to have a relatively favorable outcome.

Mammary Carcinoma Arising in Microglandular Adenosis: A Report of Five Cases.

Mammary carcinoma arising in microglandular adenosis (MGA) is extremely rare, and MGA is regarded as a non-obligate precursor of triple-negative breast cancer. We report five cases of carcinoma arising in MGA of the breast. All cases showed a spectrum of proliferative lesions ranging from MGA to atypical MGA, ductal carcinoma in situ or invasive carcinoma. Immunohistochemically, all cases were triple-negative and expression of S-100 protein gradually decreased as the lesions progressed from MGA to atypical MGA and carcinoma. Three cases showed acinic cell differentiation with reactivity to α1-antitrypsin, and one case was metaplastic carcinoma. During clinical follow-up, one patient developed local recurrence. Carcinoma arising in MGA is a rare but distinct subset of triple-negative breast cancer with characteristic histologic and immunohistochemical findings.

Metaplastic Carcinoma with Chondroid Differentiation Arising in Microglandular Adenosis.

Microglandular adenosis (MGA) of the breast is a rare, benign proliferative lesion but with a significant rate of associated carcinoma. Herein, we report an unusual case of metaplastic carcinoma with chondroid differentiation associated with typical MGA. Histologically, MGA showed a direct transition to metaplastic carcinoma without an intervening atypical MGA or ductal carcinoma in situ component. The immunohistochemical profile of the metaplastic carcinoma was mostly similar to that of MGA. In both areas, all the epithelial cells were positive for S-100 protein, but negative for estrogen receptor, progesterone receptor, HER2/neu, and epidermal growth factor receptor. An increase in the Ki-67 and p53 labelling index was observed from MGA to invasive carcinoma. To the best of our knowledge, this is the first case of metaplastic carcinoma with chondroid differentiation arising in MGA in Korea. This case supports the hypothesis that a subset of MGA may be a non-obligate morphologic precursor of breast carcinoma, especially the triple-negative subtype.

Ductal invasive carcinoma arising within atypical microglandular adenosis in a patient with BRCA-1 mutation: A case report

Microglandular adenosis (MGA) of the breast is a benign lesion that may mimic invasive carcinoma and which has been proposed to be a potential precursor of a well defined subset of triple-negative and basal-like breast carcinomas, characterized by specific expression of both basal and luminal markers (positive for EGFr and luminal cytokeratins such as CK 8/18, negative for high molecular weight cytokeratins such as CK 5/6), with a crucial role played by p53 mutation as “driver mutation” in the multistep model of cancerization. When an invasive carcinoma arises in a background of MGA, it is possible to identify a clear multistep transition from conventional MGA to atypical MGA (AMGA), Ductal Carcinoma In Situ (DCIS) arising within AMGA and invasive carcinoma. This is the first histological case report of an invasive carcinoma arising within MGA and AMGA in a patient carrying a germline BRCA-1 mutation, recognized as one of the most important genetic alterations correlated with the development of triple-negative carcinoma.

Microglandular adenosis: a prime suspect in triple-negative breast cancer development.

Microglandular adenosis (MGA) and atypical MGA (AMGA) are unusual lesions of the breast. They were once regarded as benign proliferative lesions and innocent bystanders. Several lines of evidence suggested that they could be neoplastic, clonal lesions and a non-obligate precursor for triple-negative breast cancers (TNBC). Recent work published in The Journal of Pathology by Guerini-Rocco and colleagues provided further evidence regarding the precursor-product relationship between MGA/AMGA and TNBC. Using a massively parallel sequencing approach, they demonstrated that MGA/AMGA, particularly those associated with TNBC, could be clonal neoplastic lesions showing clonal non-synonymous mutations, but none in pure MGA. Importantly, those alterations were observed in the associated TNBC. They were also able to identify recurrent alterations in TP53 in those MGA/AMGA cases as well as their associated TNBC. The findings, in conjunction with others, underscore the significance for MGA in clinical diagnosis. The potential of a benign lesion to progress into an aggressive malignant tumour implies that modification of the current management approach may be necessary. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations.

Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells. There is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the genomic landscape of pure MGA and of MGA, atypical MGA (AMGA) and associated TNBCs, and to determine whether synchronous MGA, AMGA, and TNBCs would be clonally related. Two pure MGAs and eight cases of MGA and/or AMGA associated with in situ or invasive TNBC were collected, microdissected, and subjected to massively parallel sequencing targeting all coding regions of 236 genes recurrently mutated in breast cancer or related to DNA repair. Pure MGAs lacked clonal non-synonymous somatic mutations and displayed limited copy number alterations (CNAs); conversely, all MGAs (n = 7) and AMGAs (n = 3) associated with TNBC harboured at least one somatic non-synonymous mutation (range 3-14 and 1-10, respectively). In all cases where TNBCs were analyzed, identical TP53 mutations and similar patterns of gene CNAs were found in the MGA and/or AMGA and in the associated TNBC. In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified. At diagnosis, MGAs associated with TNBC were found to display subclonal populations, and clonal shifts in the progression from MGA to AMGA and/or to TNBC were observed. Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute non-obligate precursors of TNBCs.

Bridge The Distance Between Breast Pathologists: When The Senopath Network Opens Up To The Telepathology

Introduction/ Background In clinical practice, pathologists commonly face breast lesions, which are difficult to diagnose and which re- quire discussion. In Midi-Pyrenees, the largest region ofFrance, this problem has led us to develop in 2011 a peer group for breast diseases entitled SENOPATH. Aims In order to reduce second opinion delay, erase geographical barrier and provide continuing education, we aimed to introduce an effective online and outline telepathology system in the SENOPATH network. Methods A case review by SENOPATH can be requested by any pathologist in the Midi-Pyrenees region, by filling a form through the ONCOMIP network (organization dedicated to oncology in the Midi- Pyrenees region). The slides are sent for digitalization at The University Cancer Institute - Oncopole, using a Hamamatsu 2.0-RS scanner (until 2014) and a 3DHISTECH Pannoramic 250 scanner, then anonymized and transferred to a shared storage space at Toulouse Paul Sabatier University. Virtual slides can be seen before and/or after the meeting by members of the group by login in the online 3DHISTECHCaseCentervia the Imag’IN platform website. The group, who meets on a monthly basis, has recently developed a synchronized webinar (using 3DHISTECH Case Center and Pannoramic Viewer) coupled with a conference call in order to ease the attendance of pathologists from remote pathology laboratories. A consensual diagnosis and final pathology report are issued for each case and sent to the referent clinician via the patient medical file securely hosted by ONCOMIP. Results From January 2012 to December 2015, 211 cases (39 in 2012, 50 in 2013, 75 in 2014 and 47 in 2015) have been reviewed during 43 meetings. Ten out of 43 meetings (23%) used telepathology. Sixty-one cases out of 211 (29%) were actually digitalized, mainly using theHamamatsu2.0-RS scanner. In average, the number of attending pathologists was9 to 10from 2012 to 2015. The average number of cases reviewed per meeting was 3 in 2012 and 5 between 2013 and 2015. Two main motives for review were identified: diagnostic ‘routine difficulty’ (equivocal or discordant cases, invasive vs in situ lesion, atypical vs malignant lesions, immunohistochemistry scoring pitfalls) or rare tumours. The rare tumour category included among others syringomatous tumour of the nipple, low-grade adenosquamous, myoepithelial, mucoepidermoid or secretory carcinomas, adenomyoepithelioma, atypical microglandular adenosis, sclerosing papillary hyperplasia without myoepithelium and periductal stromal tumour. Molecular analyses requested by the group and implemented in the diagnosis process mainly included immunohistochemistry and fluorescence in situ hybridization (HER2, ETV6, MAML2, MYB). The SENOPATH network committee review for difficult or rare lesions of the breast has considerably improved the pathologist’s network in our region. This working group is regularly requested by oncologists to solve difficult cases. Our aims for the next few years are 1/ to digitalize all of the cases reviewed by the SENOPATH network, 2/ to use telepathology facilities provided by the Imag’IN platform in order to widen the group to a national level, and 3/ to construct a growing online library of virtual slides for breast challenging lesions.

Breast lesions of uncertain malignant nature and limited metastatic potential: proposals to improve their recognition and clinical management.

Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are classified traditionally into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey zone between benign and malignant, as their behaviour cannot be predicted reliably. Defined pathological categorization of such lesions is challenging, and for some entities is recognized to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over- or undertreatment. The rarity of these lesions makes the acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision-making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification and behaviour, and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential, such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions of uncertain malignant nature remain, such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of (1) breast lesions of uncertain malignant nature and (2) breast lesions of limited metastatic potential are proposed with details of which histological entities could be included in each category, and their management implications are discussed.

Acinic Cell Carcinoma of the Breast Arising in Microglandular Adenosis

Acinic cell carcinoma is a rare breast tumour belonging to salivary gland-like tumours of the breast. They are “triple-negative” breast cancers even if their biological behaviour seems to be more favourable. Herein we present an acinic cell carcinoma arising on a background of typical and atypical microglandular adenosis in a 58-year-old woman, along with a review of the literature.

Molecular evidence in support of the neoplastic and precursor nature of microglandular adenosis

Microglandular adenosis (MGA) is a proliferative breast lesion, which has been proposed to be a potential precursor of triple-negative breast cancers. The aims of this study were to determine whether MGAs harbour genetic alterations and if any such genetic aberrations found in MGAs are similar to those found in matched invasive carcinomas. Twelve cases of MGA and/or atypical MGA (AMGA), 10 of which were associated with invasive carcinoma, were evaluated. Immunohistochemical profiling revealed that all invasive carcinomas were of triple-negative phenotype and expressed S100, cytokeratins 8/18 and 'basal' markers. The morphologically distinct components of each case (MGA, AMGA and/or invasive carcinoma) were microdissected and subjected to microarray comparative genomic hybridization. Apart from three typical MGAs, all samples harboured genetic alterations. The percentage of the genome affected by copy number aberrations in MGA/AMGA ranged from 0.5 to 61.9%, indicating varying levels of genetic instability. In three cases, MGA/AMGA displayed copy number aberrations similar to those found in matched invasive components, providing strong circumstantial evidence that MGA may constitute the substrate for the invasive carcinoma development. Our results support the contention that MGA can be a clonal lesion and non-obligate precursor of triple-negative breast cancer.

Atypical microglandular adenosis presenting as a breast lump

Microglandular adenosis is a rare, benign, glandular proliferative breast lesion, which also has a more atypical form. It may mimic malignancy clinically, mammographically and pathologically. Histology shows proliferation of glands with an infiltrative pattern and absence of a myoepithelial cell layer, which leads to diagnostic difficulty. We report a case of atypical microglandular adenosis diagnosed in a 78-year-old woman. The typical histological features, differential diagnostic considerations and association with malignancy are discussed.

Young-aged woman with invasive ductal carcinoma arising in atypical microglandular adenosis: A case report

Microglandular adenosis (MGA) and atypical microglandular adenosis (AMGA) are extremely rare and unique forms of adenosis of the breast. Both forms of adenosis are strongly associated with carcinoma arising in microglandular adenosis (MGACA) and are recognised as precursor lesions of invasive breast carcinoma. Here we provide a clinical report of a young Taiwanese woman who was diagnosed with MGACA and AMGA by means of echo-guided core biopsy. The subsequent lumpectomy revealed a spectrum of lesions ranging from MGA and AMGA to ductal carcinoma in situ (DCIS) and invasive carcinoma. All of the above lesions have similar immunohistochemical results (expression of S-100 protein, the absence of oestrogen receptors, progesterone receptors and Her2/neu, and the lack of p63 and the smooth muscle myosin-heavy chain) with a rather different Ki-67 labelling proliferation index. This report is of practical interest because the diagnosis of AMGA and MGACA had already been made via needle biopsy.

Invasive Breast Carcinoma Arising in Microglandular Adenosis: A Case Report and Review of the Literature

Microglandular adenosis of the breast is an extremely rare, benign lesion. Carcinoma arising in microglandular adenosis has been reported in up to 27% of patients with microglandular adenosis. We reported a case of invasive carcinoma arising in microglandular adenosis. A lumpectomy was performed on a 42-year-old female because of a mass in the right breast. Grossly, the lesion was ill-defined with thickened areas. Histologically, this case was consistent with carcinoma arising in microglandular adenosis and showed clear transition from microglandular adenosis through atypical microglandular adenosis to in situ and invasive carcinoma. All the epithelial cells were positive for cytokeratin7, S-100 protein, but negative for estrogen receptor, progesterone receptor, and Her2/Neu. No myoepithelial cells were demonstrable with immunohistochemical staining for smooth muscle actin, muscle-specific antigen or P63. Periodic acid-Schiff staining showed the presence of a basement membrane in microglandular adenosis, atypical microglandular adenosis, in situ carcinoma and the absence in invasive carcinoma. To the best of our knowledge, this is the first reported case of carcinoma arising in microglandular adenosis in China.

Molecular Evidence for Progression of Microglandular Adenosis (MGA) to Invasive Carcinoma

Microglandular adenosis (MGA) is an uncommon, benign breast lesion that is characterized by a proliferation of small uniform, round glands lined by a single layer of epithelial cells around open lumina with haphazard infiltrative growth in fibrous and fatty breast tissue. Although MGA usually has an indolent course, there is morphologic evidence that MGA can be a precursor for the development of intraductal and invasive ductal carcinoma. To investigate the possibility of such a transition, we studied 17 cases of MGA or atypical MGA some of which had given rise to carcinoma in situ (CIS) and/or invasive ductal carcinoma using the reticulin stain, immunohistochemistry (S-100, p63, Ki-67, and p53), and a molecular approach involving microdissection and high-resolution comparative genomic hybridization and MYC chromogenic in situ hybridization. MGA and carcinomas arising from MGA were typically negative for p63 and positive for S-100 and Ki-67 and occasionally positive for p53. High-resolution comparative genomic hybridization identified recurrent gains and losses in MGA (2q+, 5q-, 8q+, and 14q-) and atypical MGA (1q+, 5q-, 8q+, 14q-, and 15q-). Some examples of MGA and carcinomas arising from MGA harbored few gross chromosomal abnormalities whereas others had considerable genetic instability with widespread aberrations affecting numerous chromosomal arms. Such widespread genetic changes, together with recurrent loss of 5q and gain of 8q were reminiscent of those reported specifically for basal-like, estrogen receptor-negative, and BRCA1-associated breast tumors. Concordant genetic alterations were identified between MGA, atypical MGA, and higher risk lesions (CIS and invasive ductal carcinoma) and in some cases there was an accumulation of genetic alterations as cases "progressed" from MGA to atypical MGA, CIS, and invasive ductal carcinoma. The molecular data suggests that MGA, atypical MGA, and carcinoma arising in MGA in a single case were clonally related. This result implicates MGA as a nonobligate precursor for the development of intraductal and invasive ductal carcinoma.

Breast Carcinoma Arising in Microglandular Adenosis: A Review of the Literature

Microglandular adenosis is widely known as a benign breast lesion that can produce a mass. It differs from other types of adenosis by having an infiltrative pattern of growth and glands lacking a myoepithelial layer. Although in every other aspect the cells lining the glands are epithelial, they stain strongly with S100 protein. Most cases of microglandular adenosis are resolved after adequate excision, but more recent data suggest that this lesion may be a precursor for carcinoma, with atypical microglandular adenosis being an intermediate lesion. Carcinomas arising in a background of microglandular adenosis, although they may be low grade, are commonly estrogen and progesterone receptor negative, in contrast to most conventional low-grade carcinomas unrelated to microglandular adenosis. They also show immunopositivity for S100 protein, similar to microglandular adenosis. Diagnostic problems include differentiating microglandular adenosis from carcinoma and assessing the extent of the carcinoma component. In this review, we discuss the histomorphologic and immunophenotypic characteristic of the spectrum of microglandular adenosis lesions with emphasis on diagnostic features distinguishing microglandular adenosis from well-differentiated carcinoma, in particular, tubular carcinoma, and assessment of surgical margins of excision in such lesions.

Microglandular adenosis with transition into adenoid cystic carcinoma of the breast.

Microglandular adenosis (MGA) is a well-recognized, if rare and incompletely characterized, entity in which carcinoma is rarely thought to develop. We report 17 cases in which patterns of adenoid cystic carcinoma (ACC) coexisted with MGA. Immunocharacterization with beta-catenin, E-cadherin, cytokeratins (AE1/AE3), epithelial membrane antigen, S-100 protein, smooth muscle actin, and vimentin was also performed. Most cases had areas of invasive ACC characterized by its defining dual-lumen types. Some cases of ACC appeared to have expanded glands intermingled within the MGA, whereas in other cases ACC formed a transition with the characteristic small, gland-like spaces of MGA. MGA and "atypical MGA" stained irregularly and similarly to that seen in myoepithelium with the three markers of myoepithelial cells in breast: S-100 protein, smooth muscle actin, and vimentin. These markers were also positive in the more solid elements of the ACC. Our study suggests that ACC may develop in a background of and in continuity with MGA. Altered myoepithelial cells appear to be the major neoplastic element in both ACC and "atypical MGA." "Atypical MGA" with transition to ACC may show histologic patterns and an immunohistochemical profile similar to that of ACC. These lesions might be best interpreted as ACC in situ. Both MGA and ACC of the breast grow in an expansile and diffusely infiltrative pattern without having significant metastatic capacity. Their unusual interaction with the surrounding stroma may play a role in this benign biologic behavior.

Carcinoma Arising in Microglandular Adenosis: An Immunohistochemical Analysis of 20 Intraepithelial and Invasive Neoplasms.

Microglandular adenosis (MGA) of the breast is an uncommon, benign lesion that may mimic invasive carcinoma and has recently been recognized as having significant premalignant potential. When carcinomas arise in MGA, there is often a transition from ordinary MGA to atypical MGA (AMGA) to carcinoma. Nineteen cases of carcinoma arising in MGA are reported: 7 invasive carcinomas, 7 intraductal carcinomas (DCIS), and 5 with both invasive and intraductal carcinoma. A single case of AMGA without carcinoma is also reported. The 20 patients ranged in age from 36 to 81 years (mean 52). The most common clinical presentation was either a palpable mass (13 patients) or a mammographic abnormality (4 patients). All 20 cases contained AMGA, and in some cases AMGA was the predominant lesion. In 18 of the 19 cases with carcinoma, there was a clear transition from AMGA to the carcinoma. Twelve cases contained ordinary MGA, but in only 2 cases was MGA a prominent component of the lesion. In contrast to ordinary MGA, the glands of AMGA were more irregularly shaped, closely packed, and cytologically atypical and tended to lack secretions. A solid, occlusive proliferation of cells in the tubules was seen in 10 cases. All 12 examples of in situ carcinoma were either grade 2 or 3 and typically showed a solid proliferation of severely atypical cells within the glands; a cribrifrom pattern was also present in 1 case. The invasive carcinomas were morphologically diverse and included 2 with a basaloid morphology and 2 metaplastic carcinomas. Various immunostains were performed, and each lesion (AMGA, in situ, and invasive carcinoma) was separately assessed for immunoreactivity. As expected, S-100 was positive in the vast majority of AMGA and in situ carcinomas and in all 12 invasive carcinomas. S-100beta was also positive in the majority of cases although the staining was weaker. Laminin and type IV collagen highlighted the basement membrane around the AMGA and in situ carcinoma and are useful stains in difficult cases. Except for a single case, ER and PR were negative in all lesions. Cytokeratin 7 (CK 7) was positive, while cytokeratin 20 (CK 20) was negative in all cases. Immunostains for CK903 showed no reactivity in any of the invasive carcinomas, in situ carcinomas, or atypical MGA but was focally present in the associated MGA in 2 of the 8 cases studied. Immunostains for MIB-1 and p53 were semiquantitatively assessed and both were positive in AMGA but tended to show a more intense staining in the carcinomas. Five cases were also studied for immunoexpression of alpha-1 antitrypsin (AAT), alpha-1 antichymotrypsin (ACTP), lysozyme, and salivary gland amylase. All 5 invasive carcinomas were positive for ACTP, though the staining was very focal in about 10% of the cells in a basaloid carcinoma. The in situ carcinoma as well as the AMGA in 4 of the 5 cases were positive for ACTP. Three of the 5 invasive carcinomas were positive for AAT in 10% to 40% of the cells. The most intense positivity for AAT and ACTP was in cells with coarsely granular apocrine appearance evident in 2 of the 5 cases. Four of the 5 invasive carcinomas were positive for lysozyme in 10% to 50% of the cancer cells; the in situ carcinoma and the associated AMGA showed similar immunoreaction in each case. None of the 5 cases showed convincing positivity for salivary gland amylase. The MGA in all 5 cases was negative for AAT and ACTP; the MGA in 1 of the 5 cases was positive for lysozyme. This study confirms the potential of MGA to develop into an invasive carcinoma, more clearly defines the features of AMGA, highlights the importance of AMGA in the evolution of carcinoma from MGA, and expands our knowledge of the immunophenotype of AMGA and the carcinomas arising from it. The diagnostic criteria briefly noted previously for diagnosis of AMGA and carcinoma arising in MGA are expanded and formally proposed. Int J Surg Pathol 8(4):303-315, 2000

Breast Carcinoma Arising in Microglandular Adenosis: A Tumor Expressing S-100 Immunoreactivity. Report of Five Cases

Abstract: Five cases of breast carcinomas arising in microglandular adenosis (MGA) are described. This type of carcinoma is rare and due to 5–100 protein positivity of the tumor cells might be misinterpreted as malignant melanoma, especially when poorly differentiated or displaying a prominent clear cell change. The distinct presence of MGA with transition through areas of atypical MGA around the carcinoma, and the cytokeratin positivity of tumor cells assist in establishing the correct diagnosis. This study also supports the observation that MGA may be associated with an increased risk for subsequent development of invasive carcinoma.